rs1044396 mediates effects of nicotine self-medication

It has been reported that cigarettes can impart some calm and clarity from racing thoughts and mental fog. Patients with schizophrenia, who often experience cognitive disorganization, are 2-4 times more likely than the general population to smoke, and also seem to prefer stronger brands of cigarettes. This is not surprising since nicotine can raise levels of dopamine indirectly via stimulation of alpha4/beta2 high affinity nicotinic acetyl choline receptors (nAChR) expressed widely in the parietal cortex of the human brain. In an open access article entitled, “Association of attentional network function with exon 5 variations of the CHRNA4 gene“, Georg Winterer and colleagues demostrate that individuals who vary in a synonymous G/A variant (rs1044396) in the CHRNA4 gene – an snp which has previously been associated with nicotine dependence – show differential brain activity in the parietal cortex. When asked to remain alert and respond to rare visual “oddball” stimuli (visual oddball detection task), subjects with the AA genotype showed robust brain activity in the parietal cortex while subjects with the GG genotype showed very little change in activity. This finding reveals where in the brain – circuits connecting to the parietal cortex – may be especially important in mediating self-medication and even in the management of side-effects in psychiatric pharmacotherapy. Although rs1044396 is not measured in my 23andMe profile, the neighboring rs3787138 showing tight LD is measured and reveals that I am a boring, middle of the road heterozygote. As such, I do admit that I could use some mind-clearing relief from time to time – but, the yellow teeth are not quite worth it.